Genome-Wide Microarray Analysis of circRNAs Revealed Novel Biomarkers for Glioma Treatment and Their Promoting Effect on Glioma Progression

PURPOSE: As a novel type of non-coding RNAs, circRNAs were found to play important roles in cancer progression. In this study, we aim to investigate genome-wide circRNAs expression and potential functions in glioma to find new therapeutic targets for glioma treatment. PATIENTS AND METHODS: A total of 92 pairs of glioma tissue samples and adjacent control samples were enrolled in this study. Microarray and bioinformatics tools were used to identify circRNAs expression in glioma. Relative expression of RNAs was validated by qRT-PCR. Cell viability and migration were measured by Cell Counting Kit-8 and wound-healing assay in U251 and SHG-44 cells. The statistical correlation and overall survival were calculated by Mann–Whitney U-test and Kaplan–Meier method. RESULTS: A total of 90 differentially expressed circRNAs were identified in glioma tissues compared to control. These circRNAs were mainly back-spliced forms chr1, chr6 and chr12 with a variable number of exons. QRT-PCR showed hsa_circ_0013520 and hsa_circ_0004379 were highly expressed in glioma tissues and cell lines. High expression of hsa_circ_0013520 and hsa_circ_0004379 was significantly correlated with tumor size (P-value < 0.001), Karnofsky Performance Status (KPS, P-value: 0.008 and 0.006) and TNM stage (P-value: 0.004 and 0.005). Moreover, patients with higher expression level of hsa_circ_0013520 and hsa_circ_0004379 had a poorer overall survival (P-value: < 0.01). Besides, loss-of-function experiments revealed that inhibition of hsa_circ_0013520 and hsa_circ_0004379 suppresses proliferation and invasion of glioma cells. CONCLUSION: The present study is the first to report that hsa_circ_0013520 and hsa_circ_0004379 were up-regulated in glioma tissues and cell lines, and their expression was positively correlated with poor clinical features of glioma patients, which may serve as novel biomarkers for glioma diagnosis and therapy.